The presence of myocardial ischemia in syndrome X (chest pain, "ischemia-like" electrocardiogram changes, and normal coronary angiograms) is uncertain possibly because, when focally distributed, it may not cause contractile dysfunction or lactate production. We measured lipid hydroperoxides (ROOHs) and conjugated dienes (CDs), two sensitive, independent markers of ischemia-reperfusion oxidative stress, in paired aortic and great cardiac vein blood samples before and after pacing-induced tachycardia in nine patients with syndrome X. Diagnostic ischemic S-T segment changes during pacing were followed by a consistent increase in ROOH and CD levels in the great cardiac vein (from 4.83 +/- 1.18 micromol/l at baseline to 7.88 +/- 1.12 micromol/l and from 0.038 +/- 0.002 to 0.051 +/- 0.003 arbitrary units, respectively, P < 0.01). In controls, ROOH and CD levels did not change after pacing. The large postpacing cardiac release of lipid peroxidation products, consistently observed in all patients and similar to that previously observed after ischemia caused by percutaneous transluminal coronary angioplasty, is consistent with an ischemic origin of syndrome X.